title: Thymoquinone prevents β-amyloid neurotoxicity in primary cultured cerebellar granule neurons.
abstract: Thymoquinone (TQ), a bioactive constituent of Nigella sativa Linn (N. sativa) has demonstrated several neuropharmacological attributes. In the present study, the neuroprotective properties of TQ were investigated by studying its anti-apoptotic potential to diminish β-amyloid peptide 1-40 sequence (Aβ1-40)-induced neuronal cell death in primary cultured cerebellar granule neurons (CGNs). The effects of TQ against Aβ1-40-induced neurotoxicity, morphological damages, DNA condensation, the generation of reactive oxygen species, and caspase-3, -8, and -9 activation were investigated. Pretreatment of CGNs with TQ (0.1 and 1 μM) and subsequent exposure to 10 μM Aβ1-40 protected the CGNs against the neurotoxic effects of the latter. In addition, the CGNs were better preserved with intact cell bodies, extensive neurite networks, a loss of condensed chromatin and less free radical generation than those exposed to Aβ1-40 alone. TQ pretreatment inhibited Aβ1-40-induced apoptosis of CGNs via both extrinsic and intrinsic caspase pathways. Thus, the findings of this study suggest that TQ may prevent neurotoxicity and Aβ1-40-induced apoptosis. TQ is, therefore, worth studying further for its potential to reduce the risks of developing Alzheimer's disease.
authors.affiliation: Nutricosmeceuticals and Nutrigenomics Programme, Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
authors.forename: Norsharina
authors.initials: N
authors.lastname: Ismail
authors.forename: Maznah
authors.initials: M
authors.lastname: Ismail
authors.forename: Musalmah
authors.initials: M
authors.lastname: Mazlan
authors.forename: Latiffah Abdul
authors.initials: LA
authors.lastname: Latiff
authors.forename: Mustapha Umar
authors.initials: MU
authors.lastname: Imam
authors.forename: Shahid
authors.initials: S
authors.lastname: Iqbal
authors.forename: Nur Hanisah
authors.initials: NH
authors.lastname: Azmi
authors.forename: Siti Aisyah Abd
authors.initials: SA
authors.lastname: Ghafar
authors.forename: Kim Wei
authors.initials: KW
authors.lastname: Chan
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000473:pathology*; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004789:Enzyme Activation / Q000187:drug effects; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D016227:Benzoquinones; D002843:Chromatin; D018696:Neuroprotective Agents; D009498:Neurotoxins; D004247:DNA; D020169:Caspases; C003466:thymoquinone